The structural requirements of the D-glucose receptors of pancreatic islet B- and A2-cells governing stimulation of insulin release and inhibition of glucagon secretion are to be explored; anomeric stereospecificity has already been demonstrated. In addition, it is proposed to define the structural requirements of the islet B-cell D-glucose transport system more precisely; the requirements may, or may not, coincide with the demands imposed by the islet B-cell glucoreceptor triggering insulin release. Monolayer islet cell cultures from normal rat pancreas, containing B- and A2-cells, will be used to monitor simultaneous insulin and glucagon responses in the first area of study; subsequently the growth and responses of monolayer cultures enriched in islet B- or A2-cells will be examined to detect alterations in the structural requirements which appear when the second hormone is absent. B-Cell enriched monolayers will also be used in the transport studies. Deoxy-, fluoro-, amino-, O-alkyl- and O-aryl- analogs of D-glucose will be synthesized as a means of introducing variations in hydrogen bonding capacity, polarity and size into the D-glucose molecule. Such analogs are necessary to implement the above studies.